The maintenance of human sleeping sickness and nagana across sub-Saharan Africa depends on cyclical transmission of trypanosomes through tsetse flies. Previous work showed that the symbiotic bacterium <i>Sodalis glossinidius</i> was involved in susceptibility to trypanosome infection. Streptozotocin (a toxic analogue of the bacterium’s main food source) has been recently shown to decrease trypanosome infection rates in the offspring of treated tsetse. In the present work streptozotocin did remove <i>S. glossinidius</i> from the offspring of treated flies but it was not possible to generate a line of tsetse free from <i>S. glossinidius</i> infection. Other potential factors involved in acquisition of trypanosome infection were then examined. A range of antioxidants or cyclic GMP were shown to prevent trypanosomes death in the tsetse midgut. The process was shown to be independent of protein synthesis as D-cysteine (an unphysiological isomer of L-cysteine) also enhanced midgut infection rates. Further experiments showed that cGMP could significantly inhibit trypanosome death when fed up to 96 h post-infection, whereas antioxidants only functioned for 48 h post-infection. Moreover it was found that maturation of established midgut infections could be regulated by environmental stimuli as well as by antioxidants. Cold shock of infected flies as well as addition of L-cysteine but not D-cysteine to the bloodmeal resulted in significant increases in maturation rates, while nitric oxide synthase inhibitors reduced maturation rates. It is concluded that reactive oxygen species play a major role in killing trypanosomes entering the tsetse midgut and that cysteine containing proteins and/or nitric oxide are essential for differentiation of established midgut infections into mammalian infective salivary gland infections.
Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:654405 |
Date | January 2005 |
Creators | Macleop, E. T. |
Publisher | University of Edinburgh |
Source Sets | Ethos UK |
Detected Language | English |
Type | Electronic Thesis or Dissertation |
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